Background and PurposeDementia with Lewy bodies (DLB) needs to be distinguished from Alzheimer’s disease (AD) because of important differences in patient management and outcome. Severe cardiac sympathetic degeneration occurs in DLB, but not in AD, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the diagnostic accuracy, in the ante-mortem differentiation of probable DLB from probable AD, of cardiac imaging with the ligand 123I-meta-iodobenzylguanidine (MIBG) which binds to the noradrenaline reuptake site, in the first multicenter study.MethodsWe performed a multicenter study in which we used 123I-MIBG scans to assess 133 patients with clinical diagnoses of probable (n = 61) or possible (n = 26) DLB or probable AD (n = 46) established by a consensus panel. Three readers, unaware of the clinical diagnosis, classified the images as either normal or abnormal by visual inspection. The heart-to-mediastinum ratios of 123I-MIBG uptake were also calculated using an automated region-of-interest based system.ResultsUsing the heart-to-mediastinum ratio calculated with the automated system, the sensitivity was 68.9% and the specificity was 89.1% to differentiate probable DLB from probable AD in both early and delayed images. By visual assessment, the sensitivity and specificity were 68.9% and 87.0%, respectively. In a subpopulation of patients with mild dementia (MMSE ≥ 22, n = 47), the sensitivity and specificity were 77.4% and 93.8%, respectively, with the delayed heart-to-mediastinum ratio.ConclusionsOur first multicenter study confirmed the high correlation between abnormal cardiac sympathetic activity evaluated with 123I-MIBG myocardial scintigraphy and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from AD, especially in patients with mild dementia.

UMIN00003419.

Aim: Although dementia with Lewy bodies (DLB) is characterized by a variety of initial symptoms, there are almost no reports of the initial symptoms of DLB assessed in a large number of cases. We retrospectively evaluated the initial symptoms of 234 participants with DLB and DLB-related symptoms at diagnosis and characterized any gender differences in the symptom profiles. Methods: This study consisted of 234 participants with probable DLB who met the diagnostic criteria outlined in the Fourth Consensus Report of the DLB Consortium (2017). DLB was confirmed based on several characteristic biomarkers for dopamine transporter imaging with 123 IN -omegafluoropropyl-2-beta-carbomethoxy-3-beta (4-iodophenyl) nortropane singlephoton emission computed tomography, 123 I-metaiodobenzylguanidine myocardial scintigraphy, and brain perfusion measured with single photon emission computed tomography. In addition, core and supportive clinical features were considered in the diagnosis. Results: Initial symptoms included cognitive impairment (41.9%) and psychiatric symptoms (i.e. visual and auditory hallucinations, delusions, and depression) (42.3%). Almost half of the women initially presented with psychiatric symptoms, with significantly more women than men presenting with auditory hallucinations. In contrast, men had a significantly higher rate of rapid eye movement sleep behaviour disorder (RBD) than women did. At diagnosis, DLB-related symptoms differed between men and women, with male patients exhibiting significantly more RBD, parkinsonism, hyposmia, and syncope than female patients. Moreover women presented significantly more often with auditory hallucinations than did men. Conclusions: Our results indicate that there are gender differences in the initial symptoms of DLB, as well as in the presentation of subsequent symptoms observed at diagnosis. There was a higher incidence of RBD in men, whereas women had a higher incidence of psychotic symptoms.

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Alzheimer's disease (AD) differs from other forms of dementia in its relation to amyloid beta peptide (Abeta). Abeta, a proteolytic product of amyloid precursor proteins (APP), has a toxic effect on neuronal cells, which involves perturbation of their Ca(2+) homeostasis. This effect implies that changes of protein expression in neuronal cells with calcium stress should provide a molecular marker for this disease. In the present study, we used the supernatant from a neuronal cell culture after incubation with or without Abeta and isolated a Ca(2+)-dependent acidic phospholipid binding fraction to perform a proteomic study. Several unique proteins were identified after incubation with Abeta. We focused on annexin A5, among these proteins, because it binds both Ca(2+) and lipids likely to be involved in calcium homeostasis. Tg2576 transgenic mice (AD model) overexpressing mutant human APP showed a significant increase of annexin A5 in the brain cortex but not in other organs, including liver, kidney, lung, and intestine. In human plasma samples, the level of annexin A5 was significantly increased in a proportion of AD patients compared with a control group (P < 0.0001 in the logistic regression analysis). From the receiver operating characteristic (ROC) curve with plasma annexin A5 concentrations, the mean area under the curve (AUC 0.898) suggests that annexin A5 is a favorable marker for AD.